Cells Of Various Origins Research Articles

H4K20me3-Mediated Repression of Inflammatory Genes is a Characteristic and Targetable Vulnerability of Persister Cancer Cells.

Anti-cancer therapies can induce cellular senescence, which is highly stable, or drug-tolerant persistence, which is efficiently reversed upon therapy termination. While approaches to target senescent cells have been extensively studied, further understanding of the processes regulating persistence is needed to develop treatment strategies to suppress persister cell survival. Here, we used mTOR/PI3K inhibition to develop and characterize a model of persistence-associated arrest in human cancer cells of various origins. Persister and senescent cancer cells shared an expanded lysosomal compartment and hypersensitivity to BCL-XL inhibition. However, persister cells lacked other features of senescence, such as loss of lamin B1, senescence-associated β-galactosidase activity, upregulation of MHC-I, and an inflammatory and secretory phenotype (SASP). Genome-wide CRISPR/Cas9 screening for genes required for the survival of persister cells revealed that they are hypersensitive to the inhibition of one-carbon (1C) metabolism, which was validated by the pharmacological inhibition of SHMT, a key enzyme that feeds methyl groups from serine into 1C metabolism. Connecting 1C metabolism with the epigenetic regulation of transcription, the repressive heterochromatic mark H4K20me3 was enriched at the promoters of SASP and interferon response genes in persister cells, while it was absent in proliferative or senescent cells. Moreover, persister cells overexpressed the H4K20 methyltransferases KMT5B/C, and their downregulation unleashed inflammatory programs and compromised the survival of persister cells. In summary, this study defined distinctive features of persister cancer cells, identified actionable vulnerabilities, and provided mechanistic insight into their low inflammatory activity.

Therapeutic potential of mesenchymal stromal cells on morphological parameters in the hippocampus of rats with brain ischemia-reperfusion modeling

Ischemic stroke is an extremely important pathology with high mortality, in which more than 50 % of patients with occlusion of the main vessels remain disabled, despite early reperfusion therapy by thrombolysis or thrombectomy. As part of the regenerative strategy, stem cell transplantation in ischemic stroke became a new impetus. Cell therapy with the use of mesenchymal stromal cells demonstrated encouraging results regarding endogenous mechanisms of neuroregeneration in response to ischemic damage to brain structures. The aim of the research is to study the influence of mesenchymal stromal cells of various genesis, lysate of mesenchymal stromal cells obtained from Wharton’s jelly umbilical cord and citicoline on the dynamics of morphological changes in the hippocampal CA1 region of rats with acute cerebral ischemia-reperfusion according to light microscopy and micromorphometry data. The experiment was carried out using 200 male Wistar rats, which were subjected to ischemia-reperfusion by reversible 20-minute bilateral occlusion of the internal carotid arteries. Animals with modeled pathology were intravenously transplanted with mesenchymal stromal cells of various genesis (from Wharton’s jelly of the human umbilical cord, human and rat adipose tissue), and rat embryonic fibroblasts, lysate of mesenchymal stromal cells and citicoline were injected. Histological analysis of rat brain sections was performed on the 7th and 14th day of the experiment. Statistical analysis was performed using “Statistica 6.0” (StatSoft® Snc, USA). The significance of differences was assessed using the Student’s t-test and the nonparametric Mann-Whitney U test. During the study, it was found that modeled ischemia-reperfusion in rats caused almost complete degeneration of the structure of the pyramidal layer of hippocampal CA1 region, gave uniformity to the structure of the radiant layer, infiltration of microglia, contributed to the disruption of the arrangement of apical dendrite bundles and narrowing of blood vessels as a result of perivascular edema. Also, the modeled pathology reduced the total number of neuronal nuclei in the hippocampal CA1 area, the overwhelming majority of which had signs of pathological changes. Transplantation of mesenchymal stromal cells of various origins, lysate of mesenchymal stromal cells and citicoline contributed to a significant increase in the number of neuronal nuclei in the hippocampal CA1 zone and nuclei that did not undergo pathological changes. The most positive effect was found in the transplantation of mesenchymal stromal cells from human Wharton’s jelly-derived cells. Thus, both in the subacute and recovery periods of ischemic stroke in rats, the transplantation of human Wharton’s jelly-derived mesenchymal stromal cells was significantly surpassed the reference drug citicoline in its ability to reduce the number of pathologically changed nuclei by 1.5 times (p<0.05). At the same time, the number of pathologically unchanged nuclei significantly exceeded the number of nuclei with signs of karyorrhexis and karyopyknosis, so it would be advisable to use mesenchymal stromal cells of various genesis, lysate or citicoline in conditions of acute cerebral ischemia-reperfusion, taking into account their ability to reduce the volume of the infarct. In the future, an injectable drug will be created from the most effective culture of mesenchymal stromal cells in terms of cerebroprotective properties for cell therapy of patients with acute ischemic stroke.

A pH-Responsive Protein Assembly through Clustering of a Charge-Tunable Single Amino Acid Repeat.

Specific targeting of tumor cells is a key to achieving high therapeutic efficacy while minimizing off-target side effects. As a general approach to targeting diverse tumor cells, considerable attention has been paid to the tumor microenvironment, particularly its slightly acidic pH (6.5-6.8). However, existing pH-sensitive nanomaterials, based on organic polymers and proteins, often lack sufficient pH sensitivity and specificity. Here, we demonstrate a strategy to construct a pH-responsive protein assembly through clustering of a single amino acid repeat as a charge-tunable moiety. As a proof of concept, a histidine peptide with varying lengths was displayed on the surface of a ferritin assembly composed of 24 subunits by genetic fusion to a subunit. The resulting self-assembled ferritin particles, termed "pHerricle (pH-responsive ferritin particle)", were shown to exhibit a specific binding to tumor cells in response to pH changes through cooperative effects of histidine peptides. Increasing the histidine peptide length from 0 to 12 residues increased the pHerricle's cell-binding capacity by 21-fold and allowed modulation of the targetable pH range. General applicability as a tumor cell-targeting platform was shown by specific delivery of a cytotoxic cargo by the pHerricle into tumor cells of various origins in a pH-dependent manner.

Expression of the plasma membrane citrate carrier (pmCiC) in human cancerous tissues-correlation with tumour aggressiveness.

We have recently shown that cancer cells of various origins take up extracellular citrate through the plasma membrane citrate carrier (pmCiC), a specific plasma membrane citrate transporter. Extracellular citrate is required to support cancer cell metabolism, in particular fatty acid synthesis, mitochondrial activity, protein synthesis and histone acetylation. In addition, cancer cells tend to acquire a metastatic phenotype in the presence of extracellular citrate. Our recent study also showed that cancer-associated stromal cells synthesise and release citrate and that this process is controlled by cancer cells. In the present study, we evaluated the expression of pmCiC, fibroblast activation protein-α (FAP) and the angiogenesis marker cluster of differentiation 31 (CD31) in human cancer tissues of different origins. In the cohort studied, we found no correlation between disease stage and the expression of FAP or CD31. However, we have identified a clear correlation between pmCiC expression in cancer cells and cancer-associated stroma with tumour stage. It can be concluded that pmCiC is increased in cancer cells and in cancer-supporting cells in the tumour microenvironment at the later stages of cancer development, particularly at the metastatic sites. Therefore, pmCiC expression has the potential to serve as a prognostic marker, although further studies are needed.

Responses of Endothelial Progenitor Cells to Chronic and Acute Physical Activity in Healthy Individuals.

Endothelial progenitor cells (EPCs) are circulating cells of various origins that possess the capacity for renewing and regenerating the endothelial lining of blood vessels. During physical activity, in response to factors such as hypoxia, changes in osmotic pressure, and mechanical forces, endothelial cells undergo intense physiological stress that results in endothelial damage. Circulating EPCs participate in blood vessel repair and vascular healing mainly through paracrine signalling. Furthermore, physical activity may play an important role in mobilising this important cell population. In this narrative review, we summarise the current knowledge on the biology of EPCs, including their characteristics, assessment, and mobilisation in response to both chronic and acute physical activity in healthy individuals.

Stem cell therapy for cardiac regeneration: key points

Cardiovascular diseases are a leading cause of disability and mortality among the working population, necessitating the development and implementation of new, more effective treatment and rehabilitation methods for such patients, including the use of modern cellular and tissue technologies. In this review, an analysis and summary of research results over the past decades regarding the effectiveness of various types of stem cells in heart pathology were conducted. Priority directions include the search for more accessible and safe sources of stem cells, the development of new effective methods for their cultivation, and the use of scaffolds for transplantation. Given the pathogenetic mechanisms of cardiovascular pathology and myocardial regeneration, particular interest for clinical application is drawn to tissue-specific progenitors from the myocardium for replacing injured cardiomyocytes, endothelial progenitors for correcting accompanying endothelial dysfunction, and multipotent mesenchymal cells of various origins with low immunogenicity that exhibit trophic, anti-inflammatory, immunomodulatory, and anti-apoptotic effects. Questions regarding the optimal method, dose, and frequency of stem cell administration, as well as the standardization of criteria for their quality and effectiveness, remain open. Additionally, the combined use of different types of stem cells may serve as a new priority strategy in assessing the effectiveness and safety of cell therapy, especially considering the paradigm of repeated transplantation. The successful translation of obtained preclinical results into further large, well-planned, placebo-controlled clinical trials will enhance the safety and effectiveness of cell therapy for cardiovascular diseases, which is one of the current challenges of modern regenerative medicine.

Polyploidy Promotes Hypertranscription, Apoptosis Resistance, and Ciliogenesis in Cancer Cells and Mesenchymal Stem Cells of Various Origins: Comparative Transcriptome In Silico Study.

Mesenchymal stem cells (MSC) attract an increasing amount of attention due to their unique therapeutic properties. Yet, MSC can undergo undesirable genetic and epigenetic changes during their propagation in vitro. In this study, we investigated whether polyploidy can compromise MSC oncological safety and therapeutic properties. For this purpose, we compared the impact of polyploidy on the transcriptome of cancer cells and MSC of various origins (bone marrow, placenta, and heart). First, we identified genes that are consistently ploidy-induced or ploidy-repressed through all comparisons. Then, we selected the master regulators using the protein interaction enrichment analysis (PIEA). The obtained ploidy-related gene signatures were verified using the data gained from polyploid and diploid populations of early cardiomyocytes (CARD) originating from iPSC. The multistep bioinformatic analysis applied to the cancer cells, MSC, and CARD indicated that polyploidy plays a pivotal role in driving the cell into hypertranscription. It was evident from the upregulation of gene modules implicated in housekeeping functions, stemness, unicellularity, DNA repair, and chromatin opening by means of histone acetylation operating via DNA damage associated with the NUA4/TIP60 complex. These features were complemented by the activation of the pathways implicated in centrosome maintenance and ciliogenesis and by the impairment of the pathways related to apoptosis, the circadian clock, and immunity. Overall, our findings suggest that, although polyploidy does not induce oncologic transformation of MSC, it might compromise their therapeutic properties because of global epigenetic changes and alterations in fundamental biological processes. The obtained results can contribute to the development and implementation of approaches enhancing the therapeutic properties of MSC by removing polyploid cells from the cell population.

Multipotent mesenchymal stromal cells of various origins reduce reactive gliosis in the hippocampal CA1 area during acute ischemia-reperfusion of the rat brain

Neuroprotective therapy in acute cerebrovascular disorders is directly aimed at preserving neurons in the penumbra zone, but it also emphasizes the importance of gliogenesis in the affected area. Glial cells exhibit rapid reactivity and are highly sensitive to cerebral ischemic damage. Recent experimental studies have demonstrated the successful application of multipotent mesenchymal stromal cells (MMSCs) in stroke to modulate microglial activation. The aim of the study was to investigate the impact of MMSCs of different origins, MMSC lysate, and citicoline on glial components in a model of cerebral ischemia-reperfusion in rats. Materials and methods. The experiments were conducted on 190 male Wistar rats aged 4 months, weighing 160-190 g. After modeling cerebral ischemia-reperfusion through bilateral 20-minute occlusion of the internal carotid arteries, rats were intravenously administered MMSCs derived from human Wharton’s jelly, human adipose tissue, and rat Wharton’s jelly at a dose of 106 cells per animal. Other groups received fetal rat fibroblasts (106 cells/animal in 0.2 ml of physiological solution) and lysate from human Wharton’s jelly at a dose of 0.2 ml per animal. Control animals received 0.2 ml of physiological solution intravenously. The last group of rats received a single dose of the reference drug citicoline at a dose of 250 mg/kg. On the 7th and 14th days, the area and fluorescence intensity of cells expressing markers of astrocytes (GFAP), microglia (Iba1), and oligodendrocytes (Rip) were quantitatively assessed in CA1 hippocampal region slices using immunohistochemical examination and confocal microscopy. Results. On the 7th and 14th days after cerebral ischemia-reperfusion in rats, the intensity of fluorescence of GFAP-positive astrocytes and Iba1-positive microglial cells increased, indicating pronounced reactive astrogliosis and microglial activation in the CA1 region of the hippocampus. Meanwhile, ischemia-reperfusion had a significant impact on the content of Rip-positive oligodendrocytes in brain slices. The application of all treatments (transplantation of MMSCs of different origins, their lysate, or the reference drug citicoline) had a cytoprotective effect, reducing reactive astrogliosis and microgliosis both on the 7th and 14th days after injury. The best result was demonstrated with the treatment using MSCs from human Wharton’s jelly.s. Conclusion. Cerebral ischemia-reperfusion induces reactive gliosis through the activation of GFAP- and Iba1-positive glial cells in all layers of the hippocampus. The application of MSCs from human Wharton’s jelly and fetal rat fibroblasts significantly reduces its intensity on both the 7th and 14th days after injury modeling.

RESEARCH ON VARIOUS MODELS OF THE BIOLOGICAL EFFECTS OF COMPONENTS OF A COMPLEX EFFECT (PHOTOIRRADIATION; EXOSOMES OF MESENCHYMAL STEM CELLS AND NANOPARTICLES) FOR THE CORRECTION OF THE INFLAMMATORY PROCESS

RESEARCH ON VARIOUS MODELS OF THE BIOLOGICAL EFFECTS OF COMPONENTS OF A COMPLEX EFFECT (PHOTOIRRADIATION; EXOSOMES OF MESENCHYMAL STEM CELLS AND NANOPARTICLES) FOR THE CORRECTION OF THE INFLAMMATORY PROCESS

Treatment methods for peripheral nerve injuries (a literature review)

Aim: to analyze modern professional literature and summarize data on treatment methods for peripheral nerve injuries, taking into account the mechanisms of positive effects. The article presents an overview of possible methods for treatment of peripheral nerve injuries, fundamental classifications of peripheral nerve injuries, their differences are considered, pathophysiological mechanisms and the probability of spontaneous recovery depending on the degree of injury, general principles and conditions for successful regeneration of the peripheral nerve. Options, combinations, advantages and disadvantages of such surgical methods for peripheral nerve injury treatment as neurorrhaphy, autotransplantation and allotransplantation are described in detail, such terms as “small”, “large” and “critical” gaps between the nerve stumps are specified. Classifications and characteristics of conduits are described, types of synthetic conduits are considered. The use of drugs, Schwann cells, growth and neurotrophic factors, neural, embryonic and mesenchymal stem cells of various origins, exosomes of mesenchymal stem cells in the so-called “stem cell-free therapy” in treating this pathology is mentioned. Genetically modified mesenchymal stem cells, optokinetics are also noted, such physical methods for peripheral nerve injury treatment as short-term low-frequency electrical stimulation of the nerve, magnetic stimulation, low-intensity ultrasound, photobiomodulation therapy, photochemical bonding are discussed, indicating some mechanisms of their positive effects. Conclusions. Improving the quality of life and reducing the degree of disability in patients with injuries of the main nerve trunks depends on the combined use of a number of surgical, bioengineering and regenerative technologies. These involve the restoration of the anatomical continuity of the nerve, including through the use of natural or artificial elements, cellular technologies and the management of regenerative processes. Therefore, every time, a surgeon is facing a major challenge to create a combination of various means from the indicated basic components for the treatment of nerve damage in managing a particular patient. However, such a treatment approach requires proper competences of surgeons as well as specific material and technical bases in order to bring down the level of social tension in patients with injuries of the main nerve trunks.

STEM CELLS AND THEIR PARACRINE FACTORS

The literature review is devoted to the analysis of paracrine factors of stem cells of various origins.
 Emphasis is placed on the fact that the synthesis and secretions of trophic factors is characteristic not only of stem cells, but also of other cells of the body, such as cells of the liver, lungs, kidneys, both healthy and pathologically changed, for all these factors, which are produced by different cells, the proposed genetic name is cellular secretion, which qualitativelyand quantitatively differs depending on the type of producers of these factors.
 In parallel, concept of the “secretome“, which is widely used in the literature, also includes such names as conditioned environments. Humoral factors, trophic factors and exosomes. The broadest all-encom-passing term can be “secretome”, which can be characterized by different composition and activity and which can be understood as those substances that are needed by the cell for intercellular communication and interaction with other cells.
 The effect of the secretome on target cells and the characteristic production of humoral factors with significant trophic, stimulating properties, which contain a large number of growth factors, cytokines, and chemokines, which determine their use in pathology, are described.
 The specified features of the composition of the secretome, which is secreted by stem cells, depends on many conditions, such as: the origin of stem cells and the number of passages, conditions and environment of cultivation, duration of action of external factors, such as hypoxia, temperature and others.
 Unresolved questions were raised regarding secretome receipt and their application. It is believed that trophic factors, including the secretome of stem cells, are characterized by multidirectional mechanisms of influence on target cells, among which the following can be distinguished: stimulating proliferation and inhibiting apoptosis, immunosuppressive and immunostimulating, etc.

Differentiation of neurosphere after transplantation into the damaged spinal cord.

This study aimed to compare the differentiation and survival of human neural stem/progenitor cells of various origins in vitro and after transplantation into the injured spinal cord of laboratory animals. Rats with simulated spinal cord injury were transplanted with neurosphere cells obtained by directed differentiation of HUES6 cell lines. Fluorescence microscopy was used to visualize the obtained results. HUES6#1 and iPSC#1 neurospheres showed a wide range of markers associated with glial differentiation. The expression of the proliferation marker Ki67 did not exceed 25%, both in the lines of early and late neurospheres. Although neurospheres did not fully differentiate into astrocytes in vitro, they massively approached the GFAP+ astrocyte phenotype when exposed to the transplanted environment. PSC-derived neurospheres transplanted into the site of SM injury without additional growth factors showed only moderate survival, a significant degree of differentiation into astrocytes, and moderate differentiation into neurons. The difference in the survival and differentiation of HUES6#1 and iPSC#1 neurospheres, both in vitro and in vivo, can be explained by the difference in the regulatory behavior of signaling molecules corresponding to the source of origin of PSCs. Derivatives of human PSCs of various origins obtained according to the described differentiation protocol did not mature into astrocytic populations, nor did the glycogenic transition of PSC-derived NSCs occur in vitro. The study demonstrated the impact of the injured spinal cord microenvironment on the differentiation of transplanted HUES6#1 and iPSC#1 into astrocytes. The results showed that HUES6-derived neurospheres generated 90% of GFAP+ astrocytes and 5-10% of early neurons, while iPSC-derived neurospheres generated an average of 74% GFAP+ astrocytes and 5% of early neurons in vivo.

Extracellular Vesicles for Therapeutic Nucleic Acid Delivery: Loading Strategies and Challenges.

Extracellular vesicles (EVs) are membrane vesicles released into the extracellular milieu by cells of various origins. They contain different biological cargoes, protecting them from degradation by environmental factors. There is an opinion that EVs have a number of advantages over synthetic carriers, creating new opportunities for drug delivery. In this review, we discuss the ability of EVs to function as carriers for therapeutic nucleic acids (tNAs), challenges associated with the use of such carriers in vivo, and various strategies for tNA loading into EVs.

Cell Type-Specific Metabolic Response to Amino Acid Starvation Dictates the Role of Sestrin2 in Regulation of mTORC1

Targeting cancer metabolism has become one of the strategies for a rational anti-tumor therapy. However, cellular plasticity, driven by a major regulator of cellular growth and metabolism, mTORC1, often leads toward treatment resistance. Sestrin2, a stress-inducible protein, has been described as an mTORC1 inhibitor upon various types of stress signals. Immune assays and online measurements of cellular bioenergetics were employed to investigate the nature of Sestrin2 regulation, and finally, by silencing the SESN2 gene, to identify the role of induced Sestrin2 upon a single amino acid deprivation in cancer cells of various origins. Our data suggest that a complex interplay of either oxidative, energetic, nutritional stress, or in combination, play a role in Sestrin2 regulation upon single amino acid deprivation. Therefore, cellular metabolic background and sequential metabolic response dictate Sestrin2 expression in the absence of an amino acid. While deprivations of essential amino acids uniformly induce Sestrin2 levels, non-essential amino acids regulate Sestrin2 differently, drawing a characteristic Sestrin2 expression fingerprint, which could serve as a first indication of the underlying cellular vulnerability. Finally, we show that canonical GCN2-ATF4-mediated Sestrin2 induction leads to mTORC1 inhibition only in amino acid auxotroph cells, where the amino acid cannot be replenished by metabolic reprogramming.

The effect of mesenchymal stromal cells of various origins on morphology of hippocampal CA1 area of rats with acute cerebral ischemia

Every year, about 150,000 strokes occur in Ukraine, and more than 100,000 people die from the consequences of stroke and other circulatory disorders in the brain. So far, promising experimental data on the treatment of neurological dysfunction using mesenchymal stromal cells (MSCs) have been obtained. Purpose: to characterize the impact of MSCs of various origins, lysate of Wharton’s jelly-derived MSCs and citicoline on the dynamics of destructive changes in the hippocampal CA1 area of rats with model of acute cerebral ischemia according to morphometric data. Materials and methods. An experiment was performed using 4-month-old male Wistar rats, which were subjected to transient bilateral 20-minute ischemia-reperfusion (IR) of the internal carotid arteries. After modeling, the animals were injected intravenously with Wharton’s jelly-derived MSCs, human and rat adipose-derived MSCs at a dose 106 cells/animal. Other groups were intravenously injected with rat fetal fibroblasts at a dose of 106 cells/animal and lysate from Wharton’s umbilical cord MSCs at a dose of 0.2 mL/animal. Control animals were injected with 0.2 mL of saline. The last group of rats received a single dose of the reference drug citicoline at a dose of 250 mg/kg. On the 7th and 14th day, the total number of neuron nuclei per 1 mm2 brain section was counted in the hippocampal CA1 area, and the ratio of the number of intact neuron nuclei and nuclei with changes (karyorrhexis and karyopyknosis) was determined. Results. The transplantation of MSCs, lysate of Wharton’s jelly-derived MSCs, or citicoline contributed to a greater value of the number of nuclei in the hippocampal CA1 area, and the number of nuclei that did not undergo pathological changes also increased. The transplantation of Wharton’s jelly-derived MSCs had the most positive effect. The number of neuron nuclei per 1 mm2 in the hippocampal CA1 area in this group of animals approached the number of nuclei in the group of sham-operated animals. At the same time, the number of nuclei that did not undergo pathological changes significantly exceeded the number of nuclei with signs of destruction. Conclusion. A significant increase in the number of neurons without signs of pathological changes was observed in all experimental groups of rats during the modeling of ischemic brain injury after the administration of various types of studied mesenchymal stromal cells, lysate or citicoline. The most positive result in the hippocampal CA1 area was achieved after the administration of Wharton’s jelly-derived MSCs.

Evaluating anticancer properties of Withaferin A-a potent phytochemical.

Withaferin A is a C28 steroidal lactone derived from the plant Withania somnifera, commonly known as Ashwagandha. Withaferin A has received great attention for its anticancer properties noted in cancer cells of various origins. Extracts of Withania somnifera have been used in traditional Ayurvedic and Unani Indian medicine for their various pharmacological benefits. In recent years, Withania somnifera or Ashwagandha extract has become popularized as a health supplement marketed for its stress and anxiety reducing effects. Withaferin A is one of the most studied withanolides extracted from Withania somnifera that has gained great attention for its anticancer, anti-inflammatory, metabolic, and pro-apoptotic effects. Extensive in vivo and in vitro studies have depicted Withaferin A's interactions with key role players in cancerous activity of the cell to exert its pro-apoptotic effects. Withaferin A interactions with NF-κB, STAT, Hsp90, ER-α, p53, and TGF-β have noted inhibition in cancer cell proliferation and cell cycle arrest in G2/M stage, ultimately leading to apoptosis or cell death. This review highlights pro-apoptotic properties of Withaferin A including generation of reactive oxidative species, Par-4 activation, endoplasmic reticulum stress (ER) induction, and p53 activation. Analysis of Withaferin A's involvement in various oncogenic pathways leading to malignant neoplasm and its pharmacologic activity in conjunction with various cancer drugs provides promising evidence in therapeutic potential of Withaferin A as a cancer treatment.

INSULIN-PRODUCING CELLS IN THE TREATMENT OF TYPE 1 DIABETES: A LITERATURE REVIEW

This review discusses the prospects for the treatment of insulin-dependent diabetes mellitus. The use of insulin-producing cells of various origins is relevant and may in the future replace radical transplantation of the whole pancreas and transplantation of individual islets of Langerhans. The authors have paid attention to the peculiarities of obtaining stem cells by directed differentiation and proliferation of various fractions of stem cells, as well as to the prospects for their use in clinical practice. The regenerative features and possible complications of each pool of cells used are considered. Attention is paid to the phenomenon of plasticity which helps in transplantation and subsequent functioning. At the same time, general methods for isolating stem cells from niches containing the largest number of available progenitor cells, as well as the results of the introduction of insulin-producing cells, are considered.

Antitumor properties of nuclear erythroid cells

Purpose. To study suppressor and/or cytotoxic activity of the nuclear erythroid cells (NEC) against tumor cells of various origins. Material and Methods. C57Bl/6 mice and P815, L1210, B16 and L929 tumor cells were used. “Phenylhydrazine” NECs were obtained from mice with induced hemolytic anemia. “Erythropoietin” NECs were isolated from the “phenylhydrazine spleen” and further cultured in the presence of erythropoietin. Another source of NEC was neonatal mouse spleen, human and mouse fetal liver cells, and mouse bone marrow cells cultured with erythropoietin. The cytostatic effect of NEC or their supernatants was recorded by reducing proliferation of P815, L1210, B16, LLC, L929 lines. Results. The presence of pronounced direct antitumor activity was found in both NEC and their culturing products in relation to cells of various tumor lines. The suppressor effect was not specifc. Conclusion. We know about the signifcant numerical predominance of NEC during the embryo development over all other hematopoietic cells and their high suppressive potential. Therefore, it can be assumed that erythroblasts are involved in process of creating antitumor protection of a fetus during this period of life.

The Development of a Technique for Sensitizing Cells of Various Origins for Biotechnological Purposes

The functional activity stimulation of cell cultures was tested in MDBK cell culture, photobacteria AliivibriofischeriandHalobacteriumhalobium. Theaim of the investigation was to increase the ”yield” of the cells using an environmentallysafe stimulant and membrane-tropic agent that isalso safe for the experimenter. Ultrasonicwaves were used.Experimental ultrasonic exposure varied within the following limits: time from 1 to 300 sec, SATA-intensity of 0.01–2.0 W/cm2, generation frequency of 0.88 or 2.64 MHz, standing or traveling wave. The modulation frequency range was within 0.1–150 Hz. The devices used were: UST-1-01F, UST-5 and UST1.02C. The modulating generators were G3–112 and CP–110.Stimulation of MDBK cell growth was initiated by US-intensity of 0.03–0.05 W/cm2 , with an exposure of 5–30 sec.Exposure to ultrasound with an intensity of 0.2–0.4 W/cm2 (for 3 min) had a stimulating effect on bioluminescence and was associated with an increase in the growth rate ofA. fischeri. The findings indicated that 0.4 W/cm2ultrasonic intensity and modulation frequencies from 0.25 to 0.7 Hz can stimulate the growth of archaea.It was revealed that the maximum proliferation index in all cases of stimulant application was noted in cultures with minimal initial proliferative activity in the control.The authors expect thatthese results on the possibilities of acoustic continuous and modulated waves can be applied for biotechnological purposes to develop a new biotechnological method.
 Keywords: cell culture, ultrasound, proliferation, stimulation

STEM CELL TECHNOLOGIES IN THE TREATMENT OF ACUTE EXPERIMENTAL PANCREATITIS

Acute pancreatitis is one of the most life-threatening urgent surgical diseases. Endogenous intoxication is the main pathogenetic factor causing multiple organ failure in severe acute pancreatitis, which attaches particular importance to the search for new methods of its correction. The presented analysis of the literature data indicates that the development of effective methods of cell transplantation is currently in the focus of experimental research. The use of mesenchymal stromal cells in inflammatory processes is a new direction of regenerative medicine. Therapy of acute pancreatitis, based on the use of mesenchymal stromal cells of various origins, shows a convincing anti-inflammatory and anti-apoptotic effect in the experiment.